In aiding a clinician in the diagnosis of cancer, a pathologist faces two key problems. First, the pathologist must determine whether a tissue or cell sample removed from a patient is benign or malignant. Second, upon reaching a determination that the tissue or cell sample is malignant, the pathologist must then classify the aggressiveness of the cancer and determine its clinical and biological behavior.
A diagnosis of cancer must be confirmed through histological examination of a tissue or cell sample removed from a patient. Such histological examination entails tissue-staining procedures that allow the morphological features of the tissue to be readily examined under a microscope. The pathologist, after having examined the stained tissue or cell sample, makes qualitative determinations of the state of the tissue or the patient from whom the sample was removed and whether the tumor is benign or malignant. The aggressiveness, invasiveness and ability to metastasize of the tumor, which alone or together determine the tumor malignancy are, however, difficult to ascertain using standard histological techniques.
Visual examination of tissue and cell samples is increasingly being augmented by the use of an automated (computer-aided) image analysis system. A representative system includes a computer that receives a magnified digital representation of the tissue or cell sample from a camera and processes the received digital representation. Image analysis is generally used to assess the affinity of stains for various biological markers. Examples of suitable affinity stains include chromogen- or fluorophor-based in situ detection of specific antibodies directed against the estrogen receptor (ER), the progesterone receptor (PR), the HER-2/neu protein, and the epidermal growth factor receptor (EGFR).
The coupling of affinity staining and computer-aided image analysis has permitted clinicians to better select optimal therapies for their patients e.g., hormone therapy for cancers that are ER and PR positive, and receptor antagonist therapy for cancers overexpressing a particular receptor, such as antibodies directed against HER-2/neu (Herceptin), or enzyme inhibitors directed against EGFR (Iressa, Tarceva).
However, a need exists for an automatic identification and quantification of specifically stained targets or markers for the classification of the tissue or cell sample being examined.